A study on the prediction of targeted therapy efficacy in advanced lung adenocarcinoma patients with EGFR mutations using CT-based delta-radiomics model

Zekai Wu^1,2Peiyan Hua³Xiuying Chen¹Jie Lei⁴Laian Zhang²Peng Zhang^1*

• ¹Department of Radiology, The Second Hospital of Jilin University,, Changchun, Hebei Province, China
• ²Department of Radiology, Jiangyou People's Hospital, Mianyang, China
• ³Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Hebei Province, China
• ⁴The FAW General Hospital of Jilin Province, Changchun, Hebei Province, China

Objective: This study aimed to evaluate the predictive performance of integrated clinical and CTbased radiomic models for assessing targeted therapy efficacy in advanced lung adenocarcinoma patients with EGFR(epidermal growth factor receptor) mutations.: This retrospective study included 106 EGFR-mutated advanced lung adenocarcinoma patients treated with targeted therapies at the Second Hospital of Jilin University (2020-2023). Patients were classified as responders (PR) or non-responders (SD/PD) based on RECIST(Response Evaluation Criteria in Solid Tumors) 1.1 criteria, then randomly divided into training (n=74) and validation (n=32) cohorts at a 7:3 ratio. We segmented tumor regions on pre-and post-treatment CT scans using ITK-SNAP, then extracted radiomic features and applied mRMR-LASSO(Minimum Redundancy Maximum Relevance-Least Absolute Shrinkage and Selection Operator). A delta-radiomics model was developed by quantifying feature changes between treatment phases. Significant clinical predictors identified by logistic regression were integrated with radiomic features to build a combined model. Performance was assessed via AUC, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), DeLong's test, calibration curves, and decision curve analysis. Results: In the pre-treatment radiomics model, the AUC, accuracy, sensitivity, specificity, PPV, and NPV of the training cohorts were 0.751, 0.690, 0.737, 0.639, 0.683, and 0.697; in validation cohorts, these values were 0.726, 0.656, 0.778, 0.500, 0.667, and 0.636. In the delta-radiomics model, the AUC, accuracy, sensitivity, specificity, PPV, and NPV of the training cohorts were 0.906, 0.865, 0.868, 0.861, 0.868, and 0.861, versus 0.825, 0.719, 0.722, 0.714, 0.765, and 0.667 in validation. For the clinical model, the AUC, accuracy, sensitivity, specificity, PPV, and NPV of the training cohorts were 0.828, 0.729, 0.737, 0.722, 0.737, and 0.722, compared to 0.766, 0.750, 0.722, 0.786, 0.812, and 0.688 in validation. In the combined model,the AUC, accuracy, sensitivity, specificity, PPV, and NPV of the training cohorts were 0.977, 0.946, 0.947, 0.944, 0.947, and 0.944, while in the validation cohorts, these values were 0.913, 0.781, 0.778, 0.786, 0.824, and 0.733.The combined model integrating delta-radiomics with clinical predictors demonstrates superior predictive performance for evaluating targeted therapy efficacy in EGFR-mutated advanced lung adenocarcinoma, significantly outperforming conventional radiomics models relying exclusively on pre-treatment imaging data.